Longitudinal analysis of palatal volume in unilateral cleft lip and palate children

Cleft lip and/or palate are among the most frequent congenital craniofacial defects, which every year affect one in 500-700 newborn worldwide (1,2). The aim of this study was to analyze the effect of orthopaedic and surgical treatments on the palatal size and shape of patients with unilateral cleft lip and palate (UCLP). Ninetysix palatal casts from 32 neonatal patients, attending the Fundacion Clinica de Noel (Colombia) were analyzed through a stereophotogrammetric system. The analysis was carried out before (mean age 10.5 days, SD 4.8) and after (mean age 83.3 days, SD 6.6) orthopaedic treatment (performed with acrylic plates) and after cheiloplasty (mean age 317.1 days, SD 44.2). Volumes of the greater and the minor alveolar segments were evaluated through a new measurement protocol. Intra and inter operator repeatability was evaluated using paired Student\u2019s t test. In order to investigate differences between alveolar segments and time, volume measurements were compared with a repeated two-way analysis of variance (ANOVA). No significant differences between repetitions, both intra and inter operator, were found (p>0.05). Random errors explained 3.7% of the sample variance. On the other hand, significant differences in volume measurements were found both in alveolar segment and time (p<0.01). Before orthopaedic treatment, the smaller palatal segment had a mean volume of 0.52 cm3 (SD 0.23), and the greater of 0.9 cm3 (SD 0.40); after orthopaedic treatment, the mean volumes were 0.58 cm3 (SD 0.25), and 1.09 cm3 (SD 0.43). After surgery, mean values of 0.73 cm3 (SD 0.28) and 1.31 cm3 (SD 0.52) were measured. Results suggest that a three-dimensional stereophotogrammetric system is a repeatable and reliable method to evaluate palatal casts of patients with UCLP. Obtained data offer a preliminary quantitative information about the changes occurring in maxillary arches of UCLP patients after orthopaedic treatment and surgery. Further investigation is required to increase the frequency of evaluations and the number of patients

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

Evaluation of a 3D stereophotogrammetric technique to measure the stone casts of patients with unilateral cleft lip and palate

Objective : To assess a three-dimensional stereophotogrammetric method for palatal cast digitization of children with unilateral cleft lip and palate. Design : As part of a collaboration between the University of Milan (Italy) and the University CES of Medellin (Colombia), 96 palatal cast models obtained from neonatal patients with unilateral cleft lip and palate were obtained and digitized using a three-dimensional stereophotogrammetric imaging system. Main Outcome Measures : Three-dimensional measurements (cleft width, depth, length) were made separately for the longer and shorter cleft segments on the digital dental cast surface between landmarks, previously marked. Seven linear measurements were computed. Systematic and random errors between operators' tracings, and accuracy on geometric objects of known size were calculated. In addition, mean measurements from three-dimensional stereophotographs were compared statistically with those from direct anthropometry. Results : The three-dimensional method presented good accuracy error ( .05). Statistically significant differences (p < 5%) were noted for different methods (caliper versus stereophotogrammetry) for almost all distances analyzed, with mean absolute difference values ranging between 0.22 and 3.41 mm. Therefore, rates for the technical error of measurement and relative error magnitude were scored as moderate for Ag-Am and poor for Ag-Pg and Am-Pm distances. Generally, caliper values were larger than three-dimensional stereophotogrammetric values. Conclusions : Three-dimensional stereophotogrammetric systems have some advantages over direct anthropometry, and therefore the method could be sufficiently precise and accurate on palatal cast digitization with unilateral cleft lip and palate. This would be useful for clinical analyses in maxillofacial, plastic, and aesthetic surgery

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease

Candida Krusei, A Multidrug-Resistant Opportunistic Fungal Pathogen: Geographic and Temporal Trends From the Artemis Disk Antifungal Surveillance Program, 2001 to 2005

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Geographic and Temporal Trends in Isolation and Antifungal Susceptibility of Candida parapsilosis: a Global Assessment from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005▿

We examined data from the ARTEMIS DISK Antifungal Surveillance Program to describe geographic and temporal trends in the isolation of Candida parapsilosis from clinical specimens and the in vitro susceptibilities of 9,371 isolates to fluconazole and voriconazole. We also report the in vitro susceptibility of bloodstream infection (BSI) isolates of C. parapsilosis to the echinocandins, anidulafungin, caspofungin, and micafungin. C. parapsilosis represented 6.6% of the 141,383 isolates of Candida collected from 2001 to 2005 and was most common among isolates from North America (14.3%) and Latin America (9.9%). High levels of susceptibility to both fluconazole (90.8 to 95.8%) and voriconazole (95.3 to 98.1%) were observed in all geographic regions with the exception of the Africa and Middle East region (79.3 and 85.8% susceptible to fluconazole and voriconazole, respectively). C. parapsilosis was most often isolated from blood and skin and/or soft tissue specimens and from patients hospitalized in the medical, surgical, intensive care unit (ICU) and dermatology services. Notably, isolates from the surgical ICU were the least susceptible to fluconazole (86.3%). There was no evidence of increasing azole resistance over time among C. parapsilosis isolates tested from 2001 to 2005. Of BSI isolates tested against the three echinocandins, 92, 99, and 100% were inhibited by concentrations of ≤2 μg/ml of anidulafungin (621 isolates tested), caspofungin (1,447 isolates tested), and micafungin (539 isolates tested), respectively. C. parapsilosis is a ubiquitous pathogen that remains susceptible to the azoles and echinocandins; however, both the frequency of isolation and the resistance of C. parapsilosis to fluconazole and voriconazole may vary by geographic region and clinical service

A Next-Generation Liquid Xenon Observatory for Dark Matter and Neutrino Physics

The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for Weakly Interacting Massive Particles (WIMPs), while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector

A Next-Generation Liquid Xenon Observatory for Dark Matter and Neutrino Physics

The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for Weakly Interacting Massive Particles (WIMPs), while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector